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] | {"Title": "Protein QTL analysis of IGF-I and its binding proteins provides insights into growth biology", "Authors": "Bartell Eric, Fujimoto Masanobu, Khoury Jane C., Khoury Philip R., Vedantam Sailaja, Hirschhorn Joel, Dauber Andrew", "Abstract": "Abstract The growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGFBP-3, PAPP-A2, IGF-II, and IGFBP-5 in 839 children (3-18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near IGFBP3 and IGFBP5 genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the IGFBP3 signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the IGFBP5 signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated SNPs near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.", "URL": "https://doi.org/10.1101/2020.03.25.007724"} |
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] | {"Title": "Divide and Conquer approach for Genome Classification based on subclass characterization", "Authors": "Patil S.S., Murty M.N., Angadi U.B.", "Abstract": "Abstract Classification of large grass genome sequences has major challenges in functional genomes. The presence of motifs in grass genome chains can make the prediction of the functional behavior of grass genome possible. The correlation between grass genome properties and their motifs is not always obvious, since more than one motif may exist within a genome chain. Due to the complexity of this association most pattern classification algorithms are either vain or time consuming. Attempted to a reduction of high dimensional data that utilizes DAC technique is presented. Data are disjoining into equal multiple sets while preserving the original data distribution in each set. Then, multiple modules are created by using the data sets as independent training sets and classified into respective modules. Finally, the modules are combined to produce the final classification rules, containing all the previously extracted information. The methodology is tested using various grass genome data sets. Results indicate that the time efficiency of our algorithm is improved compared to other known data mining algorithms.", "URL": "https://doi.org/10.1101/003475"} |
10.1101/2020.03.24.005587 | [
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] | {"Title": "Machine learning pattern recognition and differential network analysis of gastric microbiome in the presence of proton pump inhibitor treatment or Helicobacter pylori infection", "Authors": "Ciucci Sara, Dur\u00e1n Claudio, Palladini Alessandra, Ijaz Umer Z., Sterbini Francesco Paroni, Masucci Luca, Cammarota Giovanni, Ianiro Gianluca, Spuul Pirjo, Schroeder Michael, Grill Stephan W., Parsons Bryony N., Pritchard D. Mark, Posteraro Brunella, Sanguinetti Maurizio, Gasbarrini Giovanni, Gasbarrini Antonio, Cannistraci Carlo Vittorio", "Abstract": "Abstract Although long thought to be a sterile and inhospitable environment, the stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of orally administered drugs such as Proton Pump Inhibitors (PPIs), or bacterial infection such as Helicobacter pylori , cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in the early phase. They mainly focus on the most prevalent taxa and rely on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques such as Principal Component Analysis and Multidimensional Scaling with nonlinear approaches derived from the physics of complex systems. Then, we show the importance to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of re-organizations which emerge from combinatorial microbial variations induced by a medical treatment (PPIs) or an infectious state ( H. pylori ).", "URL": "https://doi.org/10.1101/2020.03.24.005587"} |
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] | {"Title": "Shifts in stability and control effectiveness during evolution of paraves support aerial maneuvering hypotheses for flight origins", "Authors": "Evangelista Dennis, Cam Sharlene, Huynh Tony, Kwong Austin, Mehrabani Homayun, Tse Kyle, Dudley Robert", "Abstract": "Abstract The capacity for aerial maneuvering was likely a major influence on the evolution of flying animals. Here we evaluate consequences of paravian morphology for aerial performance by quantifying static stability and control effectiveness of physical models for numerous taxa sampled from within the lineage leading to birds (Paraves). Results of aerodynamic testing are mapped phylogenetically to examine how maneuvering characteristics correspond to tail shortening, forewing elaboration, and other morphological features. In the evolution of Paraves we observe shifts from static stability to inherently unstable aerial planforms; control effectiveness also migrated from tails to the forewings. These shifts suggest that some degree of aerodynamic control and and capacity for maneuvering preceded the evolution of strong power stroke. The timing of shifts also suggests features normally considered in light of development of a power stroke may play important roles in control.", "URL": "https://doi.org/10.1101/001750"} |
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] | {"Title": "Identification of five patterns of nucleosome positioning that globally describe transcription factor function", "Authors": "Maehara Kazumitsu, Ohkawa Yasuyuki", "Abstract": "ABSTRACT Following the binding of transcription factors (TF) to specific regions, chromatin remodeling including alterations in nucleosome positioning (NP) occurs. These changes in NP cause selective gene expression to determine cell function. However whether specific NP patterns upon TF binding determine the transcriptional regulation such as gene activation or suppression is unclear. Here we identified five patterns of NP around TF binding sites (TFBSs) using fixed MNase-Seq analysis. The most frequently observed NP pattern described the transcription state. The five patterns explained approximately 80% of the whole NP pattern on the genome in mouse C2C12 cells. We further performed ChIP-Seq using the input obtained from the fixed MNase-Seq. The result showed that a single trial of ChIP-Seq could visualize the NP patterns around the TFBS and predict the function of the transcriptional regulation at the same time. These findings indicate that NP can directly predict the function of TFs.", "URL": "https://doi.org/10.1101/003483"} |
10.1101/2020.03.25.007732 | [
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] | {"Title": "Insights into the Polyhexamethylene Biguanide (PHMB) Mechanism of Action on Bacterial Membrane and DNA: A Molecular Dynamics Study", "Authors": "Sowlati-Hashjin Shahin, Carbone Paola, Karttunen Mikko", "Abstract": "Abstract Polyhexamethylene biguanide (PHMB) is a cationic polymer with antimicrobial and antiviral properties. It has been commonly accepted that the antimicrobial activity is due the ability of PHMB to perforate the bacterial phospholipid membrane leading ultimately to its death. In this study we show by the means of atomistic molecular dynamics (MD) simulations that while the PHMB molecules attach to the surface of the phospholipid bilayer and partially penetrate it, they do not cause any pore formation at least within the microsecond simulation times. The polymers initially adsorb onto the membrane surface via the favourable electrostatic interactions between the phospholipid headgroups and the biguanide groups, and then partially penetrate the membrane slightly disrupting its structure. This, however, does not lead to the formation of any pores. The microsecond-scale simulations reveal that it is unlikely for PHMB to spontaneously pass through the phospholipid membrane. Our findings suggest that PHMB translocation across the bilayer may take place through binding to the phospholipids. Once inside the cell, the polymer can effectively \u2018bind\u2019 to DNA through extensive interactions with DNA phosphate backbone, which can potentially block the DNA replication process or activate DNA repair pathways. TOC Graphic", "URL": "https://doi.org/10.1101/2020.03.25.007732"} |
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] | {"Title": "Response to a population bottleneck can be used to infer recessive selection", "Authors": "Balick Daniel J., Do Ron, Reich David, Sunyaev Shamil R.", "Abstract": "Abstract Here we present the first genome wide statistical test for recessive selection. This test uses explicitly non-equilibrium demographic differences between populations to infer the mode of selection. By analyzing the transient response to a population bottleneck and subsequent re-expansion, we qualitatively distinguish between alleles under additive and recessive selection. We analyze the response of the average number of deleterious mutations per haploid individual and describe time dependence of this quantity. We introduce a statistic, B R , to compare the number of mutations in different populations and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. This test can be used to detect the predominant mode of selection on the genome wide or regional level, as well as among a sufficiently large set of medically or functionally relevant alleles.", "URL": "https://doi.org/10.1101/003491"} |
10.1101/2020.03.24.005603 | [
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] | {"Title": "H arvestman : A framework for hierarchical feature learning and selection from whole genome sequencing data", "Authors": "Frisby Trevor S., Baker Shawn James, Mar\u00e7ais Guillaume, Hoang Quang Minh, Kingsford Carl, Langmead Christopher James", "Abstract": "Abstract We present H arvestman , a method that takes advantage of hierarchical relationships among the possible biological interpretations and representations of genomic variants to perform automatic feature learning, feature selection, and model building. We demonstrate that H arvestman scales to thousands of genomes comprising more than 84 million variants by processing phase 3 data from the 1000 Genomes Project, the largest publicly available collection of whole genome sequences. Next, using breast cancer data from The Cancer Genome Atlas, we show that H arvestman selects a rich combination of representations that are adapted to the learning task, and performs better than a binary representation of SNPs alone. Finally, we compare H arvestman to existing feature selection methods and demonstrate that our method selects smaller and less redundant feature subsets, while maintaining accuracy of the resulting classifier. The data used is available through either the 1000 Genomes Project or The Cancer Genome Atlas. Access to TCGA data requires the completion of a Data Access Request through the Database of Genotypes and Phenotypes (dbGaP). Binary releases of H arvestman compatible with Linux, Windows, and Mac are available for download at https://github.com/cmlh-gp/Harvestman-public/releases", "URL": "https://doi.org/10.1101/2020.03.24.005603"} |
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] | {"Title": "Conformational states of the cytoprotective protein Bcl-xL", "Authors": "Ryzhov P., Tian Y., Yao Y., Bobkov A. A., Im W., Marassi F. M.", "Abstract": "ABSTRACT Bcl-xL is a major inhibitor of apoptosis, a fundamental homeostatic process of programmed cell death that is highly conserved across evolution. Because it plays prominent roles in cancer, Bcl-xL is a major target for anti-cancer therapy and for studies aimed at understanding its structure and activity. While Bcl-xL is active primarily at intracellular membranes, most studies have focused on soluble forms of the protein lacking both the membrane-anchoring C-terminal tail and the intrinsically disordered loop, and this has resulted in a fragmented view of the protein\u2019s biological activity. Here we describe how these segments affect the protein\u2019s conformation and ligand binding activity in both its soluble and membrane-anchored states. The combined data from nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and isothermal titration calorimetry (ITC) provide information about the molecular basis for the protein\u2019s functionality and a view of its complex molecular mechanisms. SIGNIFICANCE The human protein Bcl-xL is a key regulator of programmed cell death in health and disease. Structural studies, important for understating the molecular basis for its functions, have advanced primarily by deleting both the long disordered loop that regulates its activity and the C-terminal tail that anchors the protein to intracellular membranes Here we describe the preparation and conformations of full-length Bcl-xL in both its water-soluble and membrane-anchored states. The study provides new biophysical insights about Bcl-xL and its greater Bcl-2 protein family.", "URL": "https://doi.org/10.1101/2020.03.25.007740"} |
10.1101/2020.03.25.003517 | [-0.4589359760284424,0.48145928978919983,-0.6737005710601807,0.5921944379806519,-0.2613259553909302,(...TRUNCATED) | "{\"Title\": \"Structural Disconnection of the Tool Use Network After Left Hemisphere Stroke Predict(...TRUNCATED) |
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